PB2130: MAGNETISMM-6: A PHASE 3 STUDY OF ELRANATAMAB + DARATUMUMAB + LENALIDOMIDE VS DARATUMUMAB + LENALIDOMIDE + DEXAMETHASONE IN TRANSPLANT INELIGIBLE PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
Authors: Sebastian Grosicki, Su-Peng Yeh, Shang-Yi Huang, Ja Min Byun, Christine Dirienzo, Andrea Viqueira
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Elranatamab, a humanized bispecific antibody targeting B cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells, has shown promising efficacy and acceptable safety in clinical studies, as monotherapy (MagnetisMM-3, NCT04649359) and in combination with daratumumab (MagnetisMM-5, NCT05020236), in the treatment of patients with relapsed/refractory multiple myeloma (RRMM). Despite recent advances in the treatment of newly diagnosed multiple myeloma (NDMM), multiple myeloma (MM) remains incurable and more effective treatment options are needed. Aims: The aim of the MagnetisMM-6 study (NCT05623020) is to evaluate elranatamab + daratumumab + lenalidomide (EDR) versus daratumumab + lenalidomide + dexamethasone (DRd) for transplant ineligible patients with NDMM. Methods: MagnetisMM-6 is an ongoing, open-label, 2-arm, multicenter, randomized phase 3 study estimated to enroll ~646 patients. There are 2 parts: Part 1 evaluates the safety and recommended phase 3 dose (RP3D) of EDR: Part 2 evaluates the efficacy and safety of EDR at RP3D vs DRd in transplant ineligible patients with NDMM. Transplant ineligible is defined as age ≥65 or age <65 with comorbidities impacting the possibility of transplant. The primary endpoints of Part 2 are minimal residual disease (MRD) at 12 mo and progression-free survival. Secondary endpoints include overall and sustained MRD negativity rates, duration of MRD negativity, objective response rate, complete response (CR) rate, time to response, duration of response, duration of CR, overall survival, safety, quality of life, immunogenicity, and pharmacokinetics. Part 1 includes transplant ineligible patients with NDMM as well as patients with RRMM who have received 1−2 prior lines of therapy including ≥1 immunomodulatory drug and ≥1 proteasome inhibitor. Part 2 includes only transplant ineligible patients with NDMM. Key inclusion criteria are: ≥18 y; a diagnosis of MM (according to International Myeloma Working Group [IMWG] criteria); an ECOG performance status ≤2; and measurable disease based on IMWG criteria (serum M-protein ≥0.5 g/dL, urinary M-protein excretion ≥200 mg/24 hr, or involved serum free light chain [FLC] ≥100 mg/L and abnormal serum immunoglobulin κ:λ FLC ratio [<0.26 or >1.65]). Key exclusion criteria are: smoldering MM; monoclonal gammopathy; Waldenström's macroglobulinemia; plasma cell leukemia; active, uncontrolled bacterial, fungal, or viral infections; previous systemic treatment for MM (NDMM patients only); previous treatment with a BMCA-directed therapy or anti-CD38-directed therapy ≤6 mo of the first dose of study treatment (RRMM patients only); or stem cell transplant ≤3 mo of the first dose of study treatment or active graft versus host disease (RRMM patients only). As of February 2023, the study is open and enrolling at 9 sites in 5 countries. Results: N/A Keywords: Multiple myeloma, Bispecific, Clinical trial, B-cell maturation antigen